Multielectrode array analysis of cerebrospinal fluid in Alzheimer’s disease versus mild cognitive impairment: A potential diagnostic and treatment biomarker

Görtz, Philipp; Siebler, Mario; Ihl, Ralf; Henning, Ulf; Luckhaus, Christian; Supprian, Tillmann; Lange-Asschenfeldt, Christian

doi:10.1016/j.bbrc.2013.02.121

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…Acute application (15 min to 1 h) of hCSF increases neuronal activity both at a single cell and network level (Otto et al, 2009 ; Görtz et al, 2013 ; Jantzen et al, 2013 ; Björefeldt et al, 2015 ). In these previous studies, the effect of hCSF on primary cortical and mESC-derived neuronal cultures (Otto et al, 2009 ) and in acute hippocampal brain slices (Björefeldt et al, 2015 ) was studied with respect to an aCSF.…”

Section: Discussionmentioning

confidence: 99%

Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

Pérez-Alcázar

Culley

Lyckenvik

et al. 2016

Front. Cell. Neurosci.

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For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.

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Section: Discussionmentioning

confidence: 99%

Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

Pérez-Alcázar

Culley

Lyckenvik

et al. 2016

Front. Cell. Neurosci.

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“…A limitation of all previous work, including ours, is the application of hCSF obtained from unhealthy individuals. For instance, pooled CSF samples obtained from hydrocephalus patients were used as “control” CSF in all previous works ( Buddensiek et al., 2009 , Buddensiek et al., 2010 , Gortz et al., 2013 , Jantzen et al., 2013 , Koch et al., 2019 , Otto et al., 2009 , Schwarz et al., 2017 , Wickham et al., 2020 ). It has been known for decades that the chemical composition of hydrocephalus CSF differs from healthy CSF (e.g., Del Bigio, 1989 ), which indicates that these CSF samples might not be suitable to create a healthy, adult brain-like milieu in vitro .…”

Section: Discussionmentioning

confidence: 99%

Human Cerebrospinal Fluid Promotes Neuronal Circuit Maturation of Human Induced Pluripotent Stem Cell-Derived 3D Neural Aggregates

et al. 2020

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Summary Human induced pluripotent stem cell (hiPSC)-derived in vitro neural and organoid models resemble fetal, rather than adult brain properties, indicating that currently applied cultivation media and supplements are insufficient to achieve neural maturation beyond the fetal stage. In vivo , cerebrospinal fluid molecules are regulating the transition of the immature fetal human brain into a mature adult brain. By culturing hiPSC-3D neural aggregates in human cerebrospinal fluid (hCSF) obtained from healthy adult individuals, we demonstrate that hCSF rapidly triggers neurogenesis, gliogenesis, synapse formation, neurite outgrowth, suppresses proliferation of residing neural stem cells, and results in the formation of synchronously active neuronal circuits in vitro within 3 days. Thus, a physiologically relevant and adult brain-like milieu triggers maturation of hiPSC-3D neural aggregates into highly functional neuronal circuits in vitro . The approach presented here opens a new avenue to identify novel physiological factors for the improvement of hiPSC neural in vitro models.

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“…Since hippocampal and cortical rodent neuronal cultures are predominantly of glutamatergic identity, the recorded network activity in the presence of culture media or aCSF is highly synchronous ( Wagenaar et al, 2006 ; Illes et al, 2014 ; Perez-Alcazar et al, 2016 ) ( Figure 4D ). Nevertheless, hippocampal or cortical neuronal cultures exposed to healthy hCSF show a strong increase in the number of population bursts ( Otto et al, 2009 ; Gortz et al, 2013 ) ( Figure 4D ). Thus, all together these studies show that hCSF enhances neuronal activity and induces synchronicity in the network ( Otto et al, 2009 ; Gortz et al, 2013 ; Jantzen et al, 2013 ), which is consistent with the results obtained in hippocampal brain slices.…”

Section: Recent In Vitro Findings With Human Cerebmentioning

confidence: 99%

“…Nevertheless, hippocampal or cortical neuronal cultures exposed to healthy hCSF show a strong increase in the number of population bursts ( Otto et al, 2009 ; Gortz et al, 2013 ) ( Figure 4D ). Thus, all together these studies show that hCSF enhances neuronal activity and induces synchronicity in the network ( Otto et al, 2009 ; Gortz et al, 2013 ; Jantzen et al, 2013 ), which is consistent with the results obtained in hippocampal brain slices.…”

Section: Recent In Vitro Findings With Human Cerebmentioning

confidence: 99%

Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro Studies

Björefeldt

Illes

Zetterberg

et al. 2018

Front. Neural Circuits

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The cerebrospinal fluid (CSF) occupies the brain’s ventricles and subarachnoid space and, together with the interstitial fluid (ISF), forms a continuous fluidic network that bathes all cells of the central nervous system (CNS). As such, the CSF is well positioned to actively distribute neuromodulators to neural circuits in vivo via volume transmission. Recent in vitro experimental work in brain slices and neuronal cultures has shown that human CSF indeed contains neuromodulators that strongly influence neuronal activity. Here we briefly summarize these new findings and discuss their potential relevance to neural circuits in health and disease.

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Multielectrode array analysis of cerebrospinal fluid in Alzheimer’s disease versus mild cognitive impairment: A potential diagnostic and treatment biomarker

Cited by 12 publications

References 24 publications

Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

Human Cerebrospinal Fluid Promotes Neuronal Circuit Maturation of Human Induced Pluripotent Stem Cell-Derived 3D Neural Aggregates

Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro Studies

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